| 1. |
- Ahl, Rebecka, 1987-
(författare)
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The Association Between Beta-Blockade and Clinical Outcomes in the Context of Surgical and Traumatic Stress
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Traumatic injury and major abdominal surgery are areas in general surgery associated with high rates of morbidity and mortality. The overall colorectal cancer surgery mortality rate is around 4%, with that for emergency surgery more than twice as high as for planned. Surgical morbidity varies between 25% and 45%. Around half of trauma patients develop low mood. In one quarter of patients this becomes permanent. Depression is known to impede physical rehabilitation and recovery. The onset of physiological stress, driven by adrenergic hyperactivity following traumatic and surgical injury is hypothesized to contribute to these adverse outcomes. Interest has therefore been sparked into blocking adrenergic receptor activation.Papers I and II investigated the role of beta-blocker therapy in preventing post-traumatic depression following severe traumatic brain injury (Paper I) and severe extracranial injury (Paper II). The Karolinska University Hospital Trauma Registry was used to identify patients admitted between 2007 and 2011. In Paper I (n = 545), patients on pre-injury beta-blocker therapy were matched to beta-blocker naïve patients with equivalent injury burden. Results revealed that beta-blocked patients exhibited a 60% reduced risk of needing antidepressant therapy within one year of trauma. In Paper II (n = 596), the lack of beta-blocker use before extracranial trauma was linked to a three-fold increase in the risk of antidepressant initiation.Papers III-V explored the role of pre-operative beta-blocker therapy in patients undergoing surgery for colorectal cancer between 2007 and 2016, identified using the nationwide Swedish Colorectal Cancer Registry. Paper III (n = 3,187) identified a 69% reduction in the risk of 30-day mortality in beta-blocked patients. Paper IV (n = 22,337) outlined long-term survival benefits for patients on beta-blocker therapy prior to undergoing elective surgery for colon cancer. Beta-blocked patients showed a risk reduction of 42% for 1-year all-cause mortality and 18% for 5-year cancerspecific mortality. Similarly, patients on beta-blocker therapy who underwent surgery for rectal cancer demonstrated improved survival up to one year after surgery with a risk reduction of 57% and a reduction in anastomotic failure and infectious complications in Paper V (n = 11,966).
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| 2. |
- Alshamari, Muhammed, 1975-
(författare)
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Low-dose computed tomography of the abdomen and lumbar spine
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Radiography is a common radiologic investigation despite abundant evidence of its limited diagnostic value. On the other hand, computed tomography (CT) has a high diagnostic value and is widely considered to be among the most important advances in medicine. However, CT exposes patients to a higher radiation dose and it might therefore not be acceptable simply to replace radiography with CT, despite the powerful diagnostic value of this technique. At the expense of reduced CT image quality, which could be adjusted to the diagnostic needs, low-dose CT of abdomen and lumbar spine can be performed at similar dose to radiography. The aim of the current thesis project was to evaluate low-dose CT of the abdomen and lumbar spine and to compare it with radiography. The hypothesis was that CT would give better image quality and diagnostic information compared to radiography at similar dose levels. Firstly, the diagnostic accuracy of low-dose CT of the abdomen was evaluated. Results showed that low-dose CT of abdomen has a high sensitivity and specificity compared to radiography, i.e., it has higher diagnostic accuracy. Similar results were obtained from our systematic review. Secondly, in a phantom study, an ovine phantom was scanned at various CT settings. The image quality was evaluated to obtain a protocol for the optimal settings for low-dose CT of lumbar spine at 1 mSv. This new protocol was then used in a clinical study to assess the image quality of low-dose CT of the lumbar spine and compare it to radiography. Results showed that low-dose CT has significantly better image quality than radiography. Finally, the impact of Iterative reconstruction (IR) on image quality of lumbar spine CT was tested. Iterative reconstruction is a recent CT technique aimed to reduce radiation dose and/or improve image quality. The results showed that the use of medium strength IR levels in the reconstruction of CT image improves image quality compared to filtered back projection. In conclusion, low-dose CT of the abdomen and lumbar spine, at about 1 mSv, has better image quality and gives diagnostic information compared to radiography at similar dose levels and it could therefore replace radiography.
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| 3. |
- Amcoff, Karin, 1975-
(författare)
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Serological and faecal biomarkers in inflammatory bowel disease
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, are relapsing and remitting disorders characterised by chronic inflammation at various sites in the gastrointestinal tract, resulting in diarrhoea and abdominal pain. Neither the aetiology nor the pathophysiology is yet fully understood, and there is currently no cure.The overall aim of this thesis was to add a piece of the puzzle to understanding the complex pathogenesis of IBD; to determine the role of genetic and environmental factors in the development of antibodies in IBD - which could provide insight to the aetiology of the diseases; and to find sensitive and specific faecal biomarkers to predict future flare in the diseases.By conducting twin-studies, we found that some serological antibodies associated with Crohn's disease seemed to be genetically predisposed (anti-OmpC and anti-I2). Genetic predisposition do not play a predominant role in the generation of other antibodies, such as ASCA, anti-CBir1 or the autoantibody most commonly found in ulcerative colitis; pANCA. Exposure to environmental factors during childhood are suggested to be of importance in the development of ASCA and anti-CBir1 in CD. Active smoking seemed to have a protective effect against development of pANCA.Faecal calprotectin is a known marker for intestinal inflammation. In our third study, three faecal calprotectin assays were compared, which revealed overall poor agreement. This implies that standardisation of the method is highly needed.In our final study, we measured faecal eosinophil derived neurotoxin (EDN) and eosinophil cationic protein (ECP) in patients with IBD every third month over a two-year period. The results revealed that the risk of relapse in UC can be predicted by measuring EDN consecutively.
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| 4. |
- Ander, Fredrik, 1978-
(författare)
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Perioperative complications in obese patients : A thesis on risk reducing strategies
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aspiration of gastric content and delayed or failed intubation are the leading causes of anesthesia-related mortality and morbidity. In the recovery period, airway obstruction with subsequent hypoxia is a relatively common cause of morbidity, and is highly associated to the amount of opioids administered, especially in obese patients.The overall aim of this thesis was to study these risk factors for airway complications and postoperative hypoxia in obese patients, and to evaluate possible strategies for their prevention.In Study I, intubation times and incidence of failed intubation in obese patients were compared between direct laryngoscopy and videolaryngoscopy with the Stortz® C-MAC™. In Studies II and III, the effect of esmolol vs. remifentanil on the esophageal junction, and the possible analgesic properties of low-dose esmolol vs. placebo were evaluated using high-resolution manometry and the cold pressor test, respectively. Finally, in Study IV, the possible opioid-sparing effect of esmolol after laparoscopic gastric bypass surgery was evaluated.The use of videlaryngoscopy did not shorten intubation times, however appeared to reduce the incidence of failed intubation. Our results also show that esmolol has a favorable profile, compared to remifentanil, with regard to the protection against passive regurgitation and aspiration of gastric content. No analgesic effect of low-dose esmolol was however demonstrated. The intraoperative administration of esmolol instead of remifentanil also did not reduce the requirement of morphine for treatment of post-operative pain.The use of Stortz® C-MAC™ may be recommended for intubation of obese patients. Further studies are however required to clarify the possible role of esmolol in anesthesia.
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| 5. |
- Andersson, Karin, 1989-
(författare)
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Metal artifacts in computed tomography : impact of reduction methods on image quality and radiotherapy treatment planning
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Degradation of image quality by metal artifacts is a common problem in computed tomography (CT) imaging, which can limit the diagnostic value of a CT examination and also introduce inaccuracies in radiotherapy (RT) treatment planning. In recent years, commercial metal artifact reduction (MAR) methods have been launched by several CT vendors. The overall aim of this thesis was to evaluate MAR methods in diagnostic imaging and RT treatment planning.Evaluations of hip prosthesis phantom CT images showed that MAR algorithms in general improved image quality, based on both visual grading analysis and quantitative measures, while the application of virtual monoenergetic reconstructions insufficiently reduced metal artifacts. In some cases additional artifacts were introduced by the MAR algorithms. MAR algorithms were also evaluated in hip prosthesis phantom CT imaging used for proton therapy treatment planning, where improvements in dose calculation accuracy were observed.Studies of Head & Neck (H&N) implant CT images in RT treatment planning were also performed. By visual grading of anatomy visualization with respect to target delineation in dental implant patient images, MAR algorithms were shown to significantly improve image quality. However, only minor effects of H&N implant artifacts on proton dose distributions were seen. The impact might be greater for more severe artifacts than those studied here, and thus further investigations of such cases are needed.In conclusion, MAR algorithms have been shown to enhance image quality for diagnostic applications and to improve anatomy visualization in RT treatment planning. The MAR algorithms led to increased proton dose calculation accuracy in some cases, while in other situations only minor changes were seen.
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| 6. |
- Andersson, Tommy, 1970-
(författare)
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Atrial fibrillation and cause of death, sex differences in mortality, and anticoagulation treatment in low-risk patients
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Atrial fibrillation (AF) is the most common arrhythmia but information on cause of death in patients with AF is sparse, and whether individuals at low risk of cerebral infarction (CVL) should receive antico-agulant medication is controversial. Studies of sex differences with respect to mortality risk have shown conflicting results.Methods: Data were obtained from Swedish National Registers. In Study I, there were 272 186 AF patients and matched controls and in Studies II and III, 9519 AF patients and no other diagnosis and matched controls. Study IV compared treatment with warfarin to no treatment in 48 433 patients with AF. Hazard ratio (HR) was calculated with 95% confidence intervals and outcome rates as number per 1000 person-years.Results: Ischemic heart disease (IHD) was the most common underlying cause of death and was present in 40.2% of AF patients at a HR of 1.7 (1.4-2.1). CVL/stroke was a cause of death in 13.1%, HR 2.7 (1.8-4.0). Among underlying and contributing causes of death, the most common diagnoses were IHD in 43.5%, HR 1.7 (1.4-2.0) and heart failure in 33.1%, HR 2.9 (2.2-3.7). The HRs for mortality in females with AF in age categories ≤65, 65-74, and 75-85 were 2.15, 1.72, and 1.44, and for males 1.76, 1.36, and 1.24. The rates of mortality in females with AF in age categories 55-64, 65-74, and 75-85 were 6.2, 20.7, and 57.3, and for males 8.5, 27.3, and 64.5. In patients 65-74 years, females with a CHA2DS2-VASc score of 2, and males with a score of 1 receiving warfarin treatment showed a significantly reduced risk of cerebral infarc-tion/stroke, HR 0.46 (0.25-0.83) for females and for males, HR 0.39 (0.21-0.73).Conclusions: Most common causes of death in AF patients were CVL/stroke, heart failure, and IHD. HR of mortality in patients with AF was higher in females than in males but absolute risk was higher in males with AF compared to females with AF. Anticoagulant therapy was benefi-cial in patients ≥65 years, regardless of the CHA2DS2-VASc score.
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| 7. |
- Arinell, Karin, 1982-
(författare)
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Immobilization as a risk factor for arterial and venous thrombosis
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aim: Immobilization and a sedentary lifestyle are correlated with an elevated risk of both arterial and venous thrombosis. The goal of this research was to investigate whether markers associated with cardiovascular disease risk are altered during long term immobilization in a human model and in the brown bear, which survives annual cycles of long-term immobilization.Methods: In study populations assigned to 20-60 days of strict head-down-tilt bed rest 24h a day, we analysed blood levels of the emerging cardiovascular disease marker cystatin C, soluble markers of in vivo platelet activation P-selectin and PDGF-BB, and platelet aggregation. Blood samples were taken from free-ranging brown bears in summer and again during hibernation for analysis of lipid profile and platelet aggregation. Histological examination was performed on the left anterior descending coronary artery and aortic arches of bears harvested during the hunting season.Results: During prolonged bed rest in humans, levels of cystatin C and platelet aggregation remained unchanged, but we observed a significant decrease in platelet activation markers. Brown bear plasma lipids were elevated during hibernation compared with the active state and cholesterol levels were generally considerably higher than normal human values. The arterial specimens showed no signs of atherosclerosis. Platelet aggregation was halved during hibernation compared to the active state.Conclusions: Long-term immobilization has effects on several cardiovascular risk factors in both humans and bears. Increased knowledge and understanding of the protective mechanisms that allows the brown bear to survive repeated periods of immobilization could contribute to new strategies for prevention and treatment of cardiovascular disease in humans.
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| 8. |
- Asfaw Idosa, Berhane, 1977-
(författare)
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Inflammasome polymorphisms and the Inflammatory Response to Bacterial Infections
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- NLRP3 inflammasome; a key component of the innate immune system, can be activated by a number of pathogens and other threats of the body. Activation of the NLRP3 inflammasome triggers caspase-1 mediated maturationof IL-1β and IL-18. Polymorphisms Q705K and C10X are two gene variants of the NLRP3 inflammasome that combined or per se have been associated with higher risk and severity of chronic inflammation and excessive production of IL-1β. Host genetic factors have been found an important determinants of susceptibility of infectious diseases and disease outcome. The aims of this thesis were to investigate the association between polymorphisms Q705K and C10X with bacterial infections and the inflammatory response, moreover to determine the inflammasome activation state in healthy carriers of these polymorphisms. The data of the thesis show higher levels of IL-1β and IL-33 in healthy carriers of combined polymorphisms of Q705K and C10X as compared to non-carrier controls. This may provide individuals with combined polymorphisms a more robust innate immune response against pathogens, but could also lead to the onset of chronic inflammation, and excessive inflammation during acute infection. In addition, individuals with C10X polymorphism per se showed association with the presence of bacteremia as compared withhealthy blood donors. No association was found in severely ill patients with negative blood culture bottle. In addition, the results show that LOS of N. meningitidis is responsible for the priming and activating steps of the inflammasome. The non-LOS components were found to contribute to the priming step. A higher inflammatory response to N. meningitidis was found in individuals who were non-carriers of the polymorphisms than individuals with the Q705K and C10X per se or combined regardless of the strain of bacteria. Taken together, the gene variations of the NLRP3 inflammasome are of importance in explaining inter-individual variation in susceptibility to infectious diseases.
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| 9. |
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| 10. |
- Bergh, Cecilia, 1972-
(författare)
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Life-course influences on occurrence and outcome for stroke and coronary heart disease
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Although typical clinical onset does not occur until adulthood, cardiovascular disease (CVD) may have a long natural history with accumulation of risks beginning in early life and continuing through childhood and into adolescence and adulthood. Therefore, it is important to adopt a life-course approach to explore accumulation of risks, as well as identifying age-defined windows of susceptibility, from early life to disease onset. This thesis examines characteristics in adolescence and adulthood linked with subsequent risk of CVD. One area is concerned with physical and psychological characteristics in adolescence, which reflects inherited and acquired elements from childhood, and their association with occurrence and outcome of subsequent stroke and coronary heart disease many years later. The second area focuses on severe infections and subsequent delayed risk of CVD. Data from several Swedish registers were used to provide information on a general population-based cohort of men. Some 284 198 males, born in Sweden from 1952 to 1956 and included in the Swedish Military Conscription Register, form the basis of the study cohort for this thesis. Our results indicate that characteristics already present in adolescence may have an important role in determining long-term cardiovascular health. Stress resilience in adolescence was associated with an increased risk of stroke and CHD, working in part through other CVD factors, in particular physical fitness. Stress resilience, unhealthy BMI and elevated blood pressure in adolescence were also associated with aspects of stroke severity among survivors of a first stroke. We demonstrated an association for severe infections (hospital admission for sepsis and pneumonia) in adulthood with subsequent delayed risk of CVD, independent of risk factors from adolescence. Persistent systemic inflammatory activity which could follow infection, and that might persist long after infections resolve, represents a possible mechanism. Interventions to protect against CVD should begin by adolescence; and there may be a period of heightened susceptibility in the years following severe infection when additional monitoring and interventions for CVD may be of value.
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